Bリンパ球増殖・分化機構の解明とその異常制御に関する研究

白介素6最初被鉴定为T细胞源性淋巴因子，可诱导B细胞终末分化，并克隆了其基因。重组IL-6的研究证实，IL-6是B细胞产生抗体分子的必需因子之一。然而，研究表明，IL-6不仅作用于B细胞，而且在多种组织和细胞上表现出广泛的生物学功能。如作为细胞毒性T细胞分化因子作用于T细胞，作为多集落刺激因子作用于造血干细胞，作用于肝细胞诱导急性时相蛋白。IL-6具有骨髓瘤/浆细胞瘤生长因子的功能，对患者骨髓瘤细胞的实验结果表明，IL-6对骨髓瘤细胞具有自分泌生长因子的作用。携带人IL-6基因的转基因小鼠产生浆细胞瘤，证实IL-6在B系细胞中的结构性表达参与了骨髓瘤/浆细胞瘤的发生。克隆了IL-6受体的编码基因，推导的氨基酸序列表明IL-6受体属于免疫球蛋白超家族。还鉴定了与IL-6信号转导有关的第二个多肽链。克隆了淋巴细胞Fcepsilon受体(FcepsilonRII)的基因。测序结果表明，FcepsilonRII具有独特的结构，其C-末端位于分子的外侧，N-末端的一半以IgE结合因子的形式分泌，参与了过敏反应的调节。FcepsilonRII被发现与B细胞特异性分化抗原CD23相同。证明存在两种不同的FcepsilonRII，它们是通过不同的RNA剪接机制和使用不同的转录起始点而产生的。它们在胞质内的部分不同，它们的表达受到不同的调控。

Interleukin 6 was originally identified as T cell-derived lymphokine which induced final differentiation of B cells and its cDNA was cloned. The study with recombinant IL-6 confirmed that IL-6 was one of the essential factor for B cells to produce antibody molecules. However, the studies demonstrated that IL-6 acted not only on B cells but showed a wide variety of biological functions on varions tissues and cells. For example it acts on T cells as cytotoxic T cell differentiation factor, on hematopoietic stem cells as multi-colony stimulating factor, on hepatocytes to induce acute phase proteins. It functions as myeloma/plasmacytoma growth factor and the result with myeloma cells from patients demonstrated that il-6 functioned as an autocrine growth factor for myeloma cells. Transgenic mice with human IL-6 gene generated plasmacytomas confirming that constitutive expression of IL-6 in B lineage cells in involved in oncogenesis of myeloma/plasmacytoma. The cDNA encoding for IL-6 receptor was also cloned and the deduced amino acid sequence showed that IL-6 receptor belongs to immunoglobulin superfamily. A second polypeptide chain involved for IL-6 signal transduction was also identified.The cDNA for lymphocyte Fcepsilon receptor (FcepsilonRII) was cloned. The sequence showed that FcepsilonRII had an unique structure, its C-terminus outside and N-terminal half of the molecule was shown to secrete as IgE binding factor and to be involved in the regulation of allergic reactions. FcepsilonRII was found to be identical with a B cell specific differentiation antigen, CD23. The presence of two different species of FcepsilonRII which were generated by differential RNA splicing mechanism and by the usage of different transcription initiation sites, was demonstrated. They were shown to be different in their intracytoplasmic portion and their expression was differently regulated.